(3S)-pyrrolidin-3-ol → (S)-1-[(S)-1-(4-Fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-ylmethyl]-pyrrolidin-3-ol

Participants

Reaction Steps

A solution of (R)-1-(4-fluorophenyl)-6-[6-morpholin-4-yl-pyridine-3-sulfonyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carbaldehyde (0.074 g) in dry dichloroethane (2.8 mL) was treated with (S)-pyrrolidin-3-ol (0.062 g) and 4A powdered molecular sieves (0.14 g) for 4 hours. Sodium triacetoxyborohydride (0.045 g) was added and the reaction mixture stirred for 20 hours. The reaction mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution and brine. The organic extracts were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC eluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:19 to 7:3 by volume) to give the title compound as a white solid (0.025 g). 1H NMR (400 MHz, CHCl3-d): δ 8.54 (d, 1H), 8.24 (s, 1H), 7.81 (dd, 1H), 7.43-7.32 (m, 3H), 7.16 (t, 2H), 6.63 (d, 1H), 6.28 (d, 1H), 4.40 (s, 1H), 4.30 (d, 1H), 3.90 (d, 1H), 3.81 (t, 4H), 3.67 (t, 4H), 3.36-3.23 (m, 2H), 3.13-3.01 (m, 3H), 2.78-2.63 (m, 2H), 2.54 (d, 1H), 2.44-2.25 (m, 3H), 2.24-2.13 (m, 2H), 1.90 (dt, 1H).

Provenance & Evidence